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From The City of London Migraine Clinic (E.A.M., A.F.); Departments of Gynaecology and Sexual Health (E.A.M.), St Bartholomew's Hospital, London; Unipath Limited (J.E.), Priory Park, Bedford; Unilever Research (L.A.), Colworth House, Sharnbrook; and Cancer Research UK &UCL Cancer Trials Centre (A.H.), Stephenson House, London, UK.
Address correspondence and reprint requests to Dr MacGregor, The City of London Migraine Clinic, 22 Charterhouse Square, London, EC1M 6DX, UK; e-mail: anne.macgregor{at}bartsandthelondon.nhs.uk
Objective: To assess the effect of perimenstrual estradiol supplements on menstrual attacks of migraine associated with estrogen withdrawal.
Methods: Women with regular menstrual cycles and menstrual migraine or menstrually related migraine completed an initial three-cycle assessment confirming eligibility for a six-cycle crossover study using estradiol or placebo to prevent menstrual attacks of migraine. Women collected early morning samples of urine daily for laboratory assay and used a fertility monitor to identify peak fertility associated with ovulation. Estradiol gel or placebo was first applied on the tenth day following the first day of peak fertility and continued daily until, and including, the second full day of menstruation. Women kept a daily migraine diary and continued their usual treatment for migraine. The main outcome was the number of days during gel use on which a migraine occurred.
Results: Data from 35 women were available for a paired analysis. Percutaneous estradiol was associated with a 22% reduction in migraine days (RR 0.78, 95% CI 0.62 to 0.99, p = 0.04); these migraines were less severe and less likely to be associated with nausea. This was, however, followed by a 40% increase in migraine in the 5 days following estradiol vs placebo (RR 1.40, 95% CI 1.03 to 1.92, p = 0.03).
Conclusion: Although perimenstrual percutaneous estradiol showed benefit during treatment, this was offset by deferred estrogen withdrawal, triggering post-dosing migraine immediately after the gel was stopped. Further work could assess if this could be avoided by extending the duration of treatment with estradiol.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the December 26 issue to find the title link for this article.
See also page 2154
Supported by a grant from Unipath Limited.
Disclosure: E.A.M. has received consulting fees from Unipath Limited. E.A.M. and A.F. have received funding from Unipath to attend an international meeting. The City of London Migraine Clinic has received research funds from Unipath Limited. Clearblue Easy Fertility Monitors were supplied by Unipath Limited; Estreva estradiol gel was supplied by Merck-Theramex.
Received January 13, 2006. Accepted in final form September 15, 2006.
Related Articles
Neurology 2006 67: 2102-2103.
Neurology 2006 67: 2154-2158.
This article has been cited by other articles:
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  T. Pringsheim, W. J. Davenport, and D. Dodick Acute treatment and prevention of menstrually related migraine headache: Evidence-based review Neurology, April 22, 2008; 70(17): 1555 - 1563. [Abstract] [Full Text] [PDF]
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 Menstrual Migraine: The Estrogen Paradox Journal Watch Neurology, March 13, 2007; 2007(313): 2 - 2. [Full Text]
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